Diabetes has been thought to cause denervation-like changes in skeletal muscle. In this study skeletal muscle membranes were characterized in control, early and late stages of diabetes. Experimental diabetes, with a persistent hyperglycemia of 363 plus or minus 23 mg glucose/dl was induced in Sprague-Dawley rats by a single intravenous injection of streptozotocin (65 mg/kg body wt.). After 3 weeks, nerve conduction velocities decreased 25% and muscle weight decreased 50% in diabetic rats. Six days, subsequent to induction of diabetes, no significant alteration in Na, K ion(Mg ions) ATPase, Ca/Mg ions ATPase, or adenylate cyclase were observed. After 3 weeks, however, the number of Beta-adrenergic receptor sites increased from 0.37 pmol/mg plus or minus 0.01 to 0.58 pmol/mg plus or minus 0.05 with no change in the affinity constant. Na, K ion(Mg ions) ATPase and CA /Mg ions ATPase activities were also unchanged in sarcolemma and sarcoplasmic reticulum, respectively. Previous studies have shown that denervation results in a decrease in sodium fluoride- and catecholamine-stimulated adenylate cyclase activities, an increase in Na, K ion(Mg ions) ATPase activity and no change in the number and affinity of Beta-adrenergic receptor sites (Smith, P.B., et. al., Exp. Neurol. 56, 102-114, 1977). These findings demonstrate the skeletal muscle dysfunction which accompanies diabetes cannot be attributed solely to a denervation-like disease.